1. Field of the Invention
The present invention relates to the fields of opioid receptor antagonists and drug delivery. In general, particles comprising an opioid receptor antagonist are described along with methods of their use.
2. Description of Related Art
Opioids are effective analgesics. However, their use is associated with a number of undesirable side effects. One such effect is constipation. Opioid-induced changes in gastrointestinal motility are almost universal when these drugs are used to treat pain, and at times may limit their use, leaving the patient in pain. Common treatments of bulking agents and laxatives have limited efficacy and may be associated with side effects such as electrolyte imbalances.
One treatment for opioid side effects is the use of opioid receptor antagonists which cross the blood-brain-barrier, or which are administered directly into the central nervous system. Opioid receptor antagonists such as naltrexone and naloxone have been administered intramuscularly or orally to treat opioid induced side effects. Naltrexone and naloxone are highly lipid soluble and rapidly diffuse across biological membranes, including the blood-brain barrier. However, naltrexone, naloxone, nalmefene, and other opioid receptor antagonists which may reverse many opioid side effects have a narrow therapeutic window before they are observed to reverse the desired analgesic effect of the opioid being used.
Many quaternary amine opioid receptor antagonist derivatives, such as methylnaltrexone (MNTX), do not reduce the analgesic effect of opioids when administered peripheral to the central nervous system. These quaternary amine opioid receptor antagonist derivatives, which have a relatively higher polarity and reduced lipid solubility when compared to the tertiary forms of the drugs, were specifically developed to not traverse the blood-brain barrier or to traverse it at a greatly reduced rate. However, high levels of MNTX in the plasma can lead to undesirable side effects such as orthostatic hypotension.
In April 2008, the United States FDA approved the use of methylnaltrexone bromide (Relistor™) as a subcutaneous injection to help restore bowel function in patients with late-stage, advanced illness who are receiving opioids on a continuous basis to help alleviate their pain. In particular, the drug is designed to alleviate constipation in patients who have not successfully responded to laxative therapy.
Alternative methods of providing methylnaltrexone and other opioid receptor antagonists to patients are desirable, such as methods that allow lower doses of the antagonist to be delivered but with comparable efficacy, and methods less intrusive than subcutaneous injection.